Resetting mechanism for a drug delivery device

ABSTRACT

A resettable dose setting mechanism for a drug delivery device comprising a driver for driving a spindle of the drug delivery device is provided. Said driver comprises a first component and a second component rotationally coupled to said first component. During resetting of said drug delivery device, said first component is rotationally decoupled from said second component.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 13/375,183, filed on Mar. 12, 2012, which is a U.S. NationalPhase Application pursuant to 35 U.S.C. §371 of InternationalApplication No. PCT/EP2010/057483 filed May 28, 2010, which claimspriority to U.S. Provisional Patent Application No. 61/182,820 filed onJun. 1, 2009 and to European Patent Application No. 09009057.2 filed onJul. 10, 2009. The entire disclosure contents of these applications areherewith incorporated by reference into the present application.

FIELD OF INVENTION

The present application is generally directed to dose setting mechanismsfor drug delivery devices. More particularly, the present application isgenerally directed to resettable dose setting mechanisms for drugdelivery devices.

Pen type drug delivery devices provide for self administration ofmedicinal product from a multi-dose cartridge. A resettable pen typedrug delivery device allows a user to replace an empty multi-dosecartridge with a new cartridge. Consequently, the user is called upon tore-set a dose setting mechanism of the drug delivery device. Aspects ofthe invention may be equally applicable in other scenarios as well.

BACKGROUND

Pen type drug delivery devices have application where regular injectionby persons without formal medical training occurs. This may beincreasingly common among patients having diabetes where self-treatmentenables such patients to conduct effective management of their disease.

There are basically two types of pen type delivery devices: resettabledevices (i.e., reusable) and non-resettable (i.e., disposable). Thesetypes of pen delivery devices (so named because they often resemble anenlarged fountain pen) are generally comprised of three primaryelements: (i) a cartridge section that includes a cartridge oftencontained within a housing or holder; (ii) a needle assembly connectedto one end of the cartridge section; and (iii) a dosing sectionconnected to the other end of the cartridge section. A cartridge (oftenreferred to as an ampoule) typically includes a reservoir that is filledwith a medication (e.g., insulin), a movable rubber type bung or stopperlocated at one end of the cartridge reservoir, and a top having apierceable rubber seal located at the other, often necked-down, end. Acrimped annular metal band is typically used to hold the rubber seal inplace. While the cartridge housing may be typically made of plastic,cartridge reservoirs have historically been made of glass.

The needle assembly is typically a replaceable double-ended needleassembly. Before an injection, a replaceable double-ended needleassembly is attached to one end of the cartridge assembly, a dose isset, and then a dose is administered. Such removable needle assembliesmay be threaded onto, or pushed (i.e., snapped) onto the pierceable sealend of the cartridge assembly.

The dosing section or dose setting mechanism is typically the portion ofthe pen device that is used to set a dose. During an injection, aspindle contained within the dose setting mechanism presses against thebung or stopper of the cartridge. This force causes the medicationcontained within the cartridge to be injected through an attached needleassembly. After an injection, as generally recommended by most drugdelivery device and/or needle assembly manufacturers and suppliers, theneedle assembly is removed and discarded.

Different types of pen delivery devices, including disposable (i.e.,non-resettable) and reusable (i.e., resettable) varieties, have evolvedover the years. For example, disposable pen delivery devices aresupplied as self-contained devices. Such self-contained devices do nothave removable pre-filled cartridges. Rather, the pre-filled cartridgesmay not be removed and replaced from these devices without destroyingthe device itself. Consequently, such disposable devices need not have aresettable dose setting mechanism.

In contrast to typical disposable pen type devices, typical reusable pendelivery devices feature essentially two main reusable components: acartridge holder and a dose setting mechanism. After a cartridge isinserted into the cartridge holder, this cartridge holder is attached tothe dose setting mechanism. The user uses the dose setting mechanism toselect a dose. Before the user injects the set dose, a replaceabledouble-ended needle assembly is attached to the cartridge housing.

This needle assembly may be threaded onto or pushed onto (i.e., snappedonto) a distal end of the cartridge housing. In this manner, a doubleended needle mounted on the needle assembly penetrated through apierceable seal at a distal end of the cartridge. After an injection,the needle assembly is removed and discarded. After the insulin in thecartridge has been exhausted, the user detaches the cartridge housingfrom the dose setting mechanism. The user can then remove the emptycartridge from the cartridge retainer and replace the empty cartridgewith a new (filled) cartridge.

Aside from replacing the empty cartridge with a new cartridge, the usermust somehow prepare the dose setting mechanism for a new cartridge: thedose setting mechanism must be reset to a starting or initial position.For example, in certain typical resettable devices, in order to resetthe dose setting mechanism, the spindle that advances in a distaldirection during dose injection must somehow be retracted back into thedose setting mechanism. Certain known methods of retracting this spindleback into the dose setting mechanism to a restart or an initial positionare known in the art. As just one example, known reset mechanismsrequire a user to turn back or push back (retract) the spindle or someother portion of the dose setting mechanism.

Resetting of known dose setting mechanisms have certain perceiveddisadvantages. One perceived disadvantage is that the pen device userhas to disassemble the device to either remove an empty cartridge orsomehow reset the device. As such, another perceived disadvantage isthat such devices have a high number of parts and therefore such devicesare typically complicated from a manufacturing and from an assemblystandpoint. For example, certain typical resettable pen type devices arenot intuitive as to how a user must replace an empty cartridge and resetthe device. In addition, because such resettable devices use a largenumber of components parts, such resettable devices tend to be large andbulky, and therefore not easy to carry around or easy to conceal.

There is, therefore, a general need to take these disadvantagesassociated with resetting issues into consideration in the design anddevelopment of resettable drug delivery devices. Such desired drugdelivery devices would tend to reduce the number of component parts andalso tend to reduce manufacturing costs while also making the deviceless complex to assemble and manufacture. Such desired devices wouldalso tend to simplify the steps required for a user to reset a dosesetting mechanism while also making the device less complex and morecompact in size.

SUMMARY

It is an object of the present invention to provide an improvedresetting mechanism for a reusable drug delivery device.

This object is solved by a dose setting mechanism according to claim 1having a driver (e.g. drive sleeve) for driving a spindle of a drugdelivery device comprising a first component part (or portion) and asecond component part (or portion) rotationally coupled to said firstcomponent part. During resetting of the drug delivery device, the firstcomponent is rotationally decoupled from the second component. In otherwords a driver for driving a spindle of a drug delivery device,comprises a first component part; and a second component partoperatively coupled to the first component part. During a dose settingof the drug delivery device, both the first and the second componentpart rotate together. In addition, during resetting of the drug deliverydevice, the first component is decoupled from the second component andis free to rotate while the second component is prevented from rotating.The first component part may be a unitary molded component.

According to an embodiment of the invention the driver further comprisesa spindle, wherein during resetting of said drug delivery device, saidspindle is reset to an initial position. Preferably, during saidresetting of said drug delivery device, said spindle is reset to saidinitial position by moving said spindle in an axial direction. Thismovement may be an axial displacement or a combination of an axialdisplacement with a rotation, i.e. a movement on a helical path.

Decoupling of said first and second components of the driver may beachieved by moving said first component in an axial direction. Accordingto an embodiment said first component is decoupled from said secondcomponent by moving said first component in an axial direction away fromsaid second component. Alternatively, said first component may bedecoupled from said second component by moving said first component inan axially direction towards said second component.

When the device is used to inject a set dose of medication, both saidfirst component and said second component rotate and/or move in an axialdirection. Preferably, the driver (including both said first componentand said second component) does not rotate but rather moves in an axialdirection towards a distal end of said drug delivery device to therebydrive said spindle in said axial direction when said drug deliverydevice is used to inject said set dose of medication.

In another arrangement, a resettable dose setting mechanism for use witha drug delivery device comprises an outer housing and a rotating sleevein rotatable engagement with respect to the outer housing. A driverhaving a first component and a second component, said first and saidsecond component being operatively coupled together. A spindle isoperatively coupled to the drive sleeve. When a user sets a dose byrotating the rotating sleeve, both the first and second component of thedriver rotate together. When the user resets the dose setting mechanism,the first component is decoupled from the second component and the firstcomponent can rotate back to a starting position.

The dose setting mechanism may further comprise a cartridge holderreleasably coupled to said dose setting mechanism, e.g. by way of abayonet coupling. The cartridge holder may comprise a removablecartridge e.g. containing a medicament.

Irrespective of the above features, the present invention relates to adrive mechanism suitable for an injection device, comprising a housingand a pusher being movable relative to the housing with the pusher beingcoupled to the housing via first and second coupling means. The firstcoupling means comprise first engagement means of the housing and thepusher, respectively, cooperating with each other. Further, the secondcoupling means comprise a drive member, which is coupled to the pusher,and a dosing element, which is coupled to the drive member, with thedosing element being coupled to the housing via second engagement means.In addition, the drive mechanism provides for a third coupling meanscomprising a limiting element being coupled to the housing and havingthird engagement means for coupling the limiting element to the drivemember. According to the invention the second coupling means is arrangedto be decoupled at a position between the second engagement means andthe third second engagement means.

These as well as other advantages of various aspects of the presentinvention will become apparent to those of ordinary skill in the art byreading the following detailed description, with appropriate referenceto the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments are described herein with reference to thedrawings, in which:

FIG. 1 illustrates an example of a resettable drug delivery device;

FIG. 2 illustrates a further view of the first embodiment of the drugdelivery device illustrated in FIG. 1;

FIG. 3 illustrates a sectional view of the first embodiment of the drugdelivery device of FIG. 2 in a first position;

FIG. 4 illustrates a sectional view of the first embodiment of the drugdelivery device of FIG. 2 in a second position;

FIG. 5 illustrates a sectional view of the first embodiment of the drugdelivery device of FIG. 2 in a third position;

FIG. 6 illustrates a first arrangement of the driver illustrated inFIGS. 2-5 comprising a first driver portion and a second driver portion;

FIG. 7 illustrates a distal end of the spindle of the dose settingmechanism illustrated in FIGS. 2-5;

FIG. 8 illustrates a sectional view of a second embodiment of a dosesetting mechanism of the drug delivery device illustrated in FIG. 1;

FIG. 9 illustrates a partial sectional view of the second embodiment ofthe dose setting mechanism illustrated in FIG. 8;

FIG. 10 illustrates a close up view of Gap a illustrated in FIG. 8; and

FIG. 11 illustrates a second arrangement of the driver illustrated inFIGS. 6-8 comprising a first driver portion and a second driver portion.

DETAILED DESCRIPTION

The terms “drug” or “medicinal product” or “medicament”, as used herein,mean a pharmaceutical formulation containing at least onepharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a protein, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36[Asp28] Exendin-4(1-39),

des Pro36[IsoAsp28] Exendin-4(1-39),

des Pro36[Met(O)14, Asp28] Exendin-4(1-39),

des Pro36[Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36[Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36[Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36[Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36[Asp28] Exendin-4(1-39),

des Pro36[IsoAsp28] Exendin-4(1-39),

des Pro36[Met(O)14, Asp28] Exendin-4(1-39),

des Pro36[Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36[Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36[Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36[Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

H-(Lys)6-des Pro36[Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38[Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36[Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38[Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)₅-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)₆-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36[Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-(Lys)₆-NH2,

H-(Lys)₆-des Pro36, Pro37, Pro38[Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38[Met(O)14, Asp28]Exendin-4(1-39)-(Lys)₆-NH2,

H-Lys6-des Pro36[Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)₆-des Pro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)₅-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)₆-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)₅-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Referring to FIG. 1, there is shown a drug delivery device 1 inaccordance with a first arrangement of the present invention. The drugdelivery device 1 comprises a housing having a first cartridge retainingpart 2, and dose setting mechanism 4. A first end of the cartridgeretaining means 2 and a second end of the dose setting mechanism 4 aresecured together by retaining features. In this illustrated arrangement,the cartridge retaining means 2 is secured within the second end of thedose setting mechanism 4. A removable cap 3 is releasably retained overa second end or distal end of a cartridge retaining part. As will bedescribed in greater detail, the dose setting mechanism 4 comprises adose dial grip 12 and a window or lens 14. To set a dose of medicationcontained within the drug delivery device 1, a user rotates the dosedial grip 12 and the window allows a user to view the dialed dose by wayof a dose scale arrangement 16.

FIG. 2 illustrates the medical delivery device 1 of FIG. 1 with thecover 3 removed from the distal end of the medical delivery device. Asillustrated, a cartridge 20 from which a number of doses of a medicinalproduct may be dispensed is provided in the cartridge housing 6.Preferably, the cartridge 20 contains a type of medicament that must beadministered often, such as once or more times a day. One suchmedicament is insulin. A bung or stopper (not illustrated in FIG. 2, cf.cartridge piston 18 in FIG. 3) is retained in a first end or a proximalend of the cartridge 20.

The dose setting mechanism 4 of the drug delivery device illustrated inFIG. 2 may be utilized as a reusable (and hence resettable) drugdelivery device. Where the drug delivery device 1 comprises a reusabledrug delivery device, the cartridge is removable from the cartridgehousing 6. The cartridge 20 may be removed from the device withoutdestroying the device but merely by the user disconnecting the dosesetting mechanism 4 from the cartridge holder 6.

In use, once the removable cap 3 is removed, a user can attach asuitable needle assembly to the distal end of the cartridge holder. Suchneedle unit may be screwed onto a distal end of the housing oralternatively may be snapped onto this distal end. A replaceable cap 3is used to cover the cartridge holder 6 extending from the dose settingmechanism 4. Preferably, the outer dimensions of the replaceable cap 3are similar or identical to the outer dimensions of the dose settingmechanism 4 so as to provide an impression of a unitary whole when thereplaceable cap 3 is in position covering the cartridge holder 2.

FIGS. 3-5 show an example of a dose setting mechanism similar to that ofthe present invention. However, various aspects of this example,especially the general design and function of the driver, may be used inthe present invention as will become apparent to those of ordinary skillin the art.

FIG. 3 illustrates a sectional view of the dose setting mechanism 4removably connected to the cartridge holder 6. The dose settingmechanism 4 comprises an outer housing 40 containing a spindle 42, anumber sleeve 24, a clutch 26, and a driver 30. A first helical groove19 extends from a first end of a spindle 42. In one arrangement, thespindle 42 is generally circular in cross section however otherarrangements may also be used. The first end of the spindle 42 (a distalend 43 of the spindle 42) extends through a pressure plate 64. A spindlebearing 50 is located at the distal end 43 of the spindle 42. Thespindle bearing 50 is disposed to abut a second end of the cartridgepiston 18. The driver 30 extends about the spindle 42.

The clutch 26 is disposed about the driver 30, between the driver 30 anda number sleeve 24. The clutch 26 is located adjacent the second end ofthe driver 30. A number sleeve 24 is provided outside of the clutch 26and radially inward of the housing 40. The main housing 40 is providedwith a window 14 through which a part of an outer surface of the numbersleeve 10 may be viewed.

Returning to FIGS. 1-2, a dose dial grip 12 is disposed about an outersurface of the second end of the number sleeve 10. An outer diameter ofthe dose dial grip 12 preferably corresponds to the outer diameter ofthe housing 40. The dose dial grip 12 is secured to the number sleeve 10to prevent relative movement between these two components. In onepreferred arrangement, the dose dial grip 12 and number sleeve 10comprise a one piece component that is rotationally coupled to a clutchand drive sleeve and axially coupled to the number sleeve 10. However,alternative coupling arrangements may also be used.

Returning to FIGS. 3-5, in this arrangement, driver 30 comprises a firstdriver portion 44 and a second driver portion 46 and these portionsextend about the spindle 42. Both the first and the second driverportions 44, 46 are generally cylindrical. As can be seen from FIG. 6,the first drive portion 44 is provided at a first end with a firstradially extending flange 56. A second radially extending flange 58 isprovided spaced a distance along the first driver portion 44 from thefirst flange 56. An intermediate helical groove 62 is provided on anouter part of the first driver portion 44 extending between the firstflange 56 and the second flange 58. A portion or a part helical groove68 extends along an internal surface of the first driver portion 44. Thespindle 42 is adapted to work within this part helical groove 68.

A dose limiter 38 (illustrated in FIG. 3) is located between the driver30 and the housing 4, disposed between the first flange 56 and thesecond flange 58. In the illustrated arrangement, the dose limiter 38comprises a nut. The dose limiter 38 has an internal helical groovematching the helical groove 62 of the driver 30. In one preferredarrangement, the outer surface of the dose limiter 38 and an internalsurface of the housing 40 are keyed together by way of splines. Thisprevents relative rotation between the dose limiter 38 and the housing40 while allowing relative longitudinal movement between these twocomponents.

Referring back to FIGS. 2-5, essentially, in normal use, the operationof the dose setting mechanism 4 occurs as follows. To dial a dose in thearrangement illustrated in FIGS. 1-5, a user rotates the dose dial grip12. The driver 30, the clutch 26 and the number sleeve 10 rotate alongwith the dose dial grip 12.

The number sleeve 10 extends in a proximal direction away from thehousing 40. In this manner, the driver 30 climbs the spindle 42. At thelimit of travel, a radial stop on the number sleeve 10 engages either afirst stop or a second stop provided on the housing 40 to preventfurther movement. Rotation of the spindle 42 is prevented due to theopposing directions of the overhauled and driven threads on the spindle42. The dose limiter 38, keyed to the housing 40, is advanced along thethread 66 by the rotation of the driver 30.

FIG. 2 illustrates the medical delivery device after a desired dose of79 international units (IU) has been dialed. When this desired dose hasbeen dialed, the user may then dispense the desired dose of 79 IU bydepressing the dial grip 12. As the user depresses the dial grip 12,this displaces the clutch 26 axially with respect to the number sleeve10, causing the clutch 26 to disengage. However the clutch 26 remainskeyed in rotation to the driver 30. The number sleeve 10 is now free torotate.

The driver 30 is prevented from rotating with respect to the mainhousing 40 but it is free to move axially with respect thereto. Thelongitudinal axial movement of the driver 30 causes the spindle 42 torotate and thereby to advance the piston 18 in the cartridge 20.

In normal use, the first and second portions 44, 46 of the driver 30 arecoupled together when the dose dial sleeve 10 is rotated. That is, innormal use, the first and second portions 44, 46 of the driver 30 arecoupled together with the dose dial sleeve 10 when a user sets a dose byturning the dose dial grip 12. After each dispensed dose, the spindle 42is pushed in a distal direction, acting on the bung 18 of the cartridge20 to continue to expel a dialed dose of medication out of an attachedneedle assembly releasably connected to the distal end 8 of thecartridge holder 6.

After a user uses the drug delivery device 1 to dispense all of themedication contained in the cartridge 20, the user may wish to replacethe empty cartridge in the cartridge holder 6 with a new cartridge. Theuser must then also reset the dose setting mechanism 4: for example, theuser must then retract or push the spindle 42 back into the dose settingmechanism 4.

If the user decides to replace an empty cartridge and reset the device1, the first and second driver portions 44, 46 must be de-coupled fromone another. After decoupling the first driver portion 44 from thesecond driver portion 46, the first driver portion 44 will be free torotate while the second driver portion 46 will not be free to rotate.

During a device resetting step, rotating the first driver portion 44achieves at least two results. First, rotation of the first driverportion 44 will reset the axial position of the spindle 42 with respectto the dose setting mechanism 4 since rotation of the first driverportion 44 causes the spindle 42 to rotate. Rotation of the spindle 42(because the spindle is splined with the spindle guide 48) move in aproximal direction back into the dose setting mechanism. For example,FIG. 7 illustrates one arrangement for connecting the spindle 42 to thespindle guide 48. In FIG. 7, the spindle 42 comprises a first spline 51and a second spline 52. The spindle guide 48 comprises an essentiallycircular member having an aperture. The aperture includes two innerprotruding members 55, 57 that engage the first and second splines 51,52 respectively, so that the spindle guide 48 locks onto the spindle androtates along with the spindle during spindle rotation.

Second, rotation of the first driver portion 44 will also axial move orreset a dose limiter 38 to an initial or start position. That is, as thefirst driver portion 44 is rotated back to an initial start position,because the dose limiter 38 is threadedly engaged to the outer grooveand splined to an inner surface of a housing portion, such as the outerhousing 40. In this configuration, the dose limiter 38 is prevented fromrotating but will move along the outer groove 62 of the first driverportion 44 as this portion is rotated during a resetting step.

Referring to a first driver arrangement illustrated in FIG. 3, the twoportions of the driver 30 are decoupled when the first driver portion 44is pulled axially away from the second driver portion 46. This may beachieved by the use of a biasing means (such as at least one spring)that interacts together when the cartridge holder 6 is removed from thefront or distal end of the device to first lock the relative rotationbetween the spindle 42 and a spindle guide 48 through which the spindlepasses, and then to push this spindle guide 48 and also nut 66 axially afixed distance. Because the spindle 42 is rotationally locked to thisspindle guide 48 and is threadedly engaged with the spindle nut 66, thespindle 42 will move axially.

The spindle 42 is coupled via a groove engaged to the first driverportion 44. The first driver portion 44 is prevented from rotation by aclutched connection to the second driver portion 46. In one preferredarrangement, the second driver portion 46 is prevented from rotation bya clicker detent 75. The clicker detent 75 resides between the clutchand the flange 80 on the drive sleeve 46. Therefore, axial movement ofthe spindle 42 decouples the two driver portions 44, 46 so that theclutched connection becomes de-coupled.

This sequence of operation as the cartridge holder 6 is removed ordisconnected from the dose setting mechanism 4 is illustrated in FIGS.3-5. In FIG. 3, the various component parts of the drug delivery deviceinclude: a dose setting housing 40, a cartridge 20, a spindle 42, firstdriver portion 44; second driver portion 46, spindle bearing 50, spindleguide 48, a spring plate 54; a main spring 60, a pressure plate 64, acartridge holder 20; a spindle nut 66; and a second spring 70. In thispreferred arrangement, the spindle guide 48 is rotationally fixedrelative to the spindle 20. In addition, the spring plate 54, pressureplate 64 and spindle nut 66 are all rotationally fixed relative to theouter housing.

In FIG. 3, the cartridge holder 6 is fitted via apertures in thepressure plate 64 and applies a load to the spring plate 54. Thiscompresses the first biasing means or main spring 60. These apertures inthe pressure plate 64 (not shown) allow the pressure plate 64 to moveaway from the spring plate 54 (in a distal direction towards thecartridge holder 6) under the action of the second biasing means orsecond spring 70. This will open up a Gap “a” as shown in FIG. 3. Gap“a” is a gap created between the pressure plate 64 and the spring plate54. This will also open Gap “b”, a gap between the spindle nut 66 andthe spring plate 54. This Gap b is illustrated in FIG. 3. The Gap b inconjunction with the light force from the second spring or biasing means70 moves the spindle nut 66 towards the distal end of the drug deliverydevice 1. This applies light pressure to the spindle guide 48.

The spindle guide 48 is compressed under the action of the second spring70 between the spindle nut 66 and pressure plate 64. This light forcecoupled with the friction coefficient on either side of a flange of thespindle guide 48 through which this force acts, provides a resistance torotation of the spindle guide 48 and therefore a resistance to rotationof spindle 42 as well. One advantage of this configuration is that atthe end of a dose, it is advantageous to prevent the spindle 42 fromback-winding into the dose setting mechanism 4 under light residualloads that may remain from the cartridge bung 18. By preventing thespindle 42 from back-winding in a proximal direction, a distal end 43 ofthe spindle 42 (and hence the spindle bearing 50) remains on the bung18. Maintaining the distal end 43 of the spindle 42 on the bung 18 helpsto prevent a user from administrating a potential under-dose.

When the user delivers a dose, as the dispense force increases, therearward load on the spindle nut 66 increases to a point at which thespindle nut 66 travels back in a proximal direction and compresses thesecond spring 70. This releases the axial force acting on the spindleguide 48. This removes the resistance to rotation of the spindle guide48 and hence spindle 42. This configuration therefore preventsback-winding of the spindle 42 under low loads caused by the cartridgebung 18, but does not add to the dispense force once this dispense forcehas increased above a certain threshold level.

FIG. 4 illustrates the dose setting mechanism 4 of FIG. 3 with thecartridge holder 6 rotated to release a connection type between thehousing 40 of dose setting mechanism 4 and the cartridge holder 6. Inone arrangement, this connection type 22 is a bayonet connection.However, those of ordinary skill in the art will recognize that otherconnection types 22 may be used as well such as threads, snap locks,snap fits, luer locks and other similar connection types. In thearrangement illustrated in FIGS. 3-5, by rotating the cartridge holder 6with respect to housing 40, features that were initially acting on thespring plate 54 to compress the main biasing means 60 through aperturesin the pressure plate 64, rotate so that they now release this forcecreated by the main biasing means 60. This allows the spring plate 54 tomove in a distal direction until the spring plate 54 contacts thespindle nut 66 on an inside face of the spindle nut 66.

In this second condition, the previous discussed Gap “a” (from FIG. 3)has now been reduced to a Gap “c” (as seen in FIG. 4). In this manner,the relative high axial force from the main biasing means 60 actsthrough the spring plate 54 to the spindle nut 66 and from the spindlenut 66 through the spindle guide 48 to the pressure plate 64. Thisrelative high axial force from the main biasing means 60 is sufficientto prevent the spindle guide 48, and hence spindle 42, from rotating.

After sufficient rotation of the cartridge holder 6, the cartridgeholder 6 disengages from the connection type 22 with the housing 40. Thecartridge holder 6 is then driven in an axial direction away from thehousing 40 by the main biasing means 60 (i.e., in a distal direction).However, during this movement, the main spring 60 continues to load thecartridge holder 6 through the spindle guide 48 and therefore thespindle 42 is prevented from rotation. As the spindle 42 is alsothreaded to the first driver portion 44, the first driver portion 44 isalso pulled axially in a distal direction and in this manner becomesdisengaged from the second driver portion 46. The second driver portion46 is axially fixed and is prevented from rotation. In one arrangement,the second driver portion 46 is prevented from rotation by clickerelements and prevented from axial movement by its axial coupling to thenumber sleeve.

FIG. 5 illustrates the dose setting mechanism illustrated in FIG. 3 in athird position, that is, with the cartridge holder 6 removed. As thecartridge holder 6 is removed from the housing 40, the bayonet featuresshown in FIG. 5 (illustrated as round pegs extending radially inwards oninside of inner housing), limit travel of the pressure plate 64 butallows Gap “c” (as shown in FIG. 4) to increase to a wider Gap “d” (asshown in FIG. 5). As a result, Gap “e” develops. Gap “e” removes thehigh spring force created by the main biasing means 60 from the spindleguide 48. The dose setting mechanism 4 in FIG. 4 is now ready to bereset.

To reset this dose setting mechanism 4, a user retracts the spindle 42in a proximal direction back into the housing 40 by pushing on thedistal end 43 of the spindle 42. Therefore, during this resetting stepof the dose setting mechanism 4, as the spindle 42 is pushed back intothe dose setting mechanism 4, the movement of the spindle 42 causes thespindle nut 66 to move back against a light spring force created by thesecond biasing means 70. This movement releases the axial load and henceresistance to rotation from the spindle guide 48. Therefore, as the dosesetting mechanism 4 is reset by the spindle 42 rotating back into thedose setting mechanism 4, the spindle guide 48 also rotates.

As the spindle 42 is pushed back further into the dose setting mechanism4, the spindle 42 rotates through the spindle nut 66. As the firstdriver portion 44 is de-coupled from the second driver portion 46, thefirst driver portion 44 rotates (with the flexible elements 102, 103running on a conical surface groove 90 formed by the first annular ring91 on the second half of the drive sleeve 46, FIGS. 5 and 6). Thisaccommodates the axial and rotational movement of the spindle 42.

As the first driver portion 44 rotates during reset, first driverportion 44 also resets the dose nut. More specifically, as the firstdriver portion 44 rotates, the dose nut which is not rotatable since itis splined to an inner surface of the housing 40, traverses along thehelical groove 62 provided along an outer surface of the first driverportion 44 and traverses back to an initial or starting position. In onepreferred arrangement, this starting position of the dose nut residesalong the first radial 56 flange of the first driver portion 44.

After the dose setting mechanism 4 has been reset, the dose settingmechanism 4 must be re-connected to the cartridge holder 6. Whenre-connecting these two components, the process generally works inreverse. However, this time the axial compression of the main spring 60causes the first driver portion 44 to re-engage with the second driverportion 46. In this manner, the flexible elements re-engage with thesecond annular ring 94 on the second driver portion 46.

FIG. 6 illustrates a first arrangement of the second driver portion 46and the first driver portion 44 illustrated in FIG. 3. As shown in FIG.6, second driver portion 46 is generally tubular in shape and comprisesa first annular groove 90 at a distal end of the second driver portion46. The first annular groove 90 comprises a conical face 91. The seconddriver portion further comprises a second annular groove 94 and at leastone spline 96 positioned along a surface of the second driver portion.

The first driver portion 44 is also generally tubular in shape andcomprises a first and a second flexible element 102, 103 and a pluralityof spline recesses 100. These plurality of recesses 100 releasablyconnect the longitudinal spline 96 of the first driver portion 44 tosecond driver portion 46 when both first and second driver portions 44,46 are pushed axially together so that they releasably engage oneanother. When pushed together, the flexible elements 102, 103 of thefirst driver portion 44 are pushed over the first annular groove 90 ofthe second driver portion 46 and then stop when the flange 80 of thesecond driver portion abuts the first axial flange 56 of the firstdriver portion 44.

The first driver portion 44 also includes a plurality of ratchetfeatures 104. These ratchet features 104 are provided at a distal end106 of the first driver portion 44. These ratchet features 104 engagesimilar ratchet features on the spring plate 25 which are splined to thehousing 2. (See e.g., FIGS. 3-5) At the end of the resetting step, theseratchet features engage one another so as to prevent the first driverportion 44 from rotating, thereby ensuring that as the spindle 42 isreset further, the first drive portion moves axially to re-engage thesecond drive portion 46 rather than rotate on the conical face 90. Thesefeatures also orientate the spring plate 25 relative to the seconddriver portion 44 so that the two driver portions 44, 46 engage easilyduring assembly or after reset. Therefore, these ratchet features alsoprevent the coupling features 100, 96 from clashing with one another.

A second arrangement of resettable dose setting mechanism is illustratedin FIGS. 8-10. FIG. 8 illustrates a section view of a second arrangementof a dose setting mechanism 200. Those of skill in the art willrecognize that dose setting mechanism 200 may include a connectionmechanism for releasably connecting to a cartridge holder, like thecartridge holder 6 illustrated in FIG. 2. FIG. 9 illustrates a portionof the dose setting mechanism illustrating the driver operation. FIG. 10illustrates a close up view of the coupling between the first driverportion and the second driver portion illustrated in FIG. 9. The secondarrangement of the dose setting mechanism 200 operates in a similarfashion to the first arrangement of the dose setting mechanism 4illustrated in FIGS. 1-5.

With reference to FIGS. 8-10, the dose setting mechanism 200 comprises adose dial grip 202, a spring 201, a housing 204, a clutch 205, a numbersleeve 206, and an inner housing 208. Similar to the driver 30illustrated in FIGS. 2-5, driver 209 of dose setting mechanism comprisesa first driver portion 207 and a second driver portion 212. In onearrangement, the first driver portion 207 comprises a first componentpart 210 and a second component part 211. Alternatively, the firstdriver portion 207 is an integral component part.

As illustrated in FIGS. 8 and 9, the driver 209 is de-coupled from thedose setting mechanism 200 when the first driver portion 207 is pushedaxially towards the second driver portion 212 (i.e., pushed in aproximal direction). In one arrangement, this may be achieved by pushingaxially on a distal end of the spindle 214. This does not require anymechanism associated with removal of a cartridge holder. The mechanismis also designed such that the first and second driver portions 207, 212and the spindle 214 remain locked together rotationally during dosesetting as well as during dose administration.

FIGS. 4-6 illustrate the relative movement of the first driver portion44 compared to the second driver portion 46 for two different states ofthe two-piece driver. FIG. 4 shows the first driver portion 44 coupledto and rotationally fixed to the second driver portion 46. The movementindicator 300 for the second driver portion 46 and the movementindicator 301 for the first driver portion 44 indicate this. In FIG. 4,where the two driver portions are coupled together the movementindicators 300 and 301, shown as arrows, indicate that both driverportions rotate together, for example, during dose setting. FIGS. 5 and6, where the first and second driver portions are decoupled, forexample, during the resetting of the device, the movement indicator 300for the second driver portion 46 is a flat line indicating no movement,however, the movement indicator 301 for the first driver portion 44 isan arrow indicating that the first driver portion 44 can move relativeto the stationary second driver portion 46.

An axial force on the spindle 214 causes the spindle 214 to rotate dueto its threaded connection to the inner housing 208. This rotation andaxial movement of the spindle 214 in turn causes the first driverportion 207 to move axially towards the second driver portion 212. Thiswill eventually de-couple the coupling elements 250 between the firstdriver portion 207 and second driver portion 212. This can be seen fromFIG. 11.

This axial movement of the first driver portion 207 towards the seconddriver portion 212 results in certain advantages. For example, oneadvantage is that the metal spring 201 will compress and will thereforeclose the Gap a illustrated in FIGS. 8-10. This in turn prevents theclutch 205 from disengaging from the clicker 220 or from the numbersleeve 206. The second driver 212 is prevented from rotation since it issplined to the clutch 205. The clicker 220 is splined to the housing204. Therefore, when the Gap a is reduced or closed up, the seconddriver portion 212 cannot rotate relative to either the housing 204 orthe number sleeve 206. As a consequence, the number sleeve 206 cannotrotate relative to the housing 204. If the number sleeve 206 isprevented from rotating then, as the spindle 214 is refracted back intothe dose setting mechanism 200 and thereby re-set, there will be no riskof the number sleeve 206 being pushed out of the proximal side of thedose setting mechanism 200 as a result of a force being applied on thespindle 214.

Similarly, when the drug delivery device is being dispensed, the userapplies an axial load to a dose button 216. The dose button 216 isaxially coupled to the clutch 205 and this prevents relative axialmovement. Therefore, the clutch 205 moves axially towards the cartridgeend or the distal end of the dose setting mechanism 200. This movementdisengages the clutch 205 from the number sleeve 206, allowing forrelative rotation while closing up the Gap a.

As described above, this prevents the clutch 205 from rotating relativeto the clicker 220 and hence relative to the housing 204. However, inthis scenario, it also prevents the coupling between the first driverportion 210 and the second driver portion 212 from becoming disengaged.Therefore, any axial load on the spindle 214 only disengages the firstand second driver portions 207, 212 when the dose button 216 is notaxially loaded. This therefore does not happen during dispense.

With the dose setting mechanism 200, as a user dials a dose with thedose dial grip 202, the metal spring 201 is selected to be strong enoughto maintain engagement of both clutched couplings: the clutched couplingbetween the clutch 205 and the number sleeve 206 and clutched couplingbetween the first driver portion 207 and second driver portion 212.

FIG. 11 shows in detail of a first arrangement of the first driverportion 207 and the second driver portion 212 illustrated in FIG. 8. Asillustrated in FIG. 11, the second driver portion 212 is generallytubular in shape and comprises at least one drive dog 250 located at adistal end of the second driver portion 212. The first driver portion207 also has a generally tubular shape and comprises a plurality ofrecesses 252 sized to engage with the drive dog 250 on the second driverportion 212. The construction of the drive dog and recesses allowdisengagement with the drive dog 250 when the first and second driverportions are axially pushed together. This construction also creates arotational coupling when these components are sprung apart. A doselimiter 218 is provided on first driver portion 207 and operatessimilarly to the dose limiter 38 illustrated in FIG. 3.

In this arrangement, the first driver portion 207 comprises a firstportion 211 that is permanently clipped to a second portion 210. In thisarrangement, the first portion 211 comprises the drive dogs 252 and thesecond component 210 includes the outer groove for the last dose nut aswell as an internal groove 254. This internal groove 254 is used toconnect to the spindle 214 and drives the spindle 214 during doseadministration.

In the illustrated arrangement, the internal groove 254 comprises a parthelical groove rather than a complete helical groove. One advantage ofthis arrangement is that it is generally easier to manufacture.

Exemplary embodiments of the present invention have been described.Those skilled in the art will understand, however, that changes andmodifications may be made to these embodiments without departing fromthe true scope and spirit of the present invention, which is defined bythe claims.

The invention claimed is:
 1. A resettable dose setting mechanism for adrug delivery device comprising: a spindle; a rotating sleeve inrotatable engagement with respect to housing; and a driver for drivingthe spindle of the drug delivery device in a distal direction to cause adistal end of the spindle to act on a bung within a cartridge, whereinsaid driver comprises a first component and a second componentrotationally coupled to said first component, wherein during resettingof said drug delivery device, said first component is decoupled fromsaid second component such that the first component can rotate relativeto the second component causing the spindle to retract axially in aproximal direction, wherein during a dose setting operation a userrotates the rotating sleeve causing the first component and the secondcomponent of the driver to rotate together, wherein the resettable dosesetting mechanism is designed such that the first component and thesecond component remain locked together rotationally during the dosesetting operation as well as during dose administration and whereinduring the dose setting operation the first and second components arecoupled together to rotate together in unison relative to the housingand the spindle causing the driver to move axially in the proximaldirection when the user dials a dose of medicament for administration.2. The resettable dose setting mechanism of claim 1 further comprisingbiasing means causing the first component to engage with the secondcomponent.
 3. The resettable dose setting mechanism of claim 1 whereinthe first component comprises a first component part and a secondcomponent part.
 4. The resettable dose setting mechanism of claim 1wherein the first component is an integral component part.
 5. Theresettable dose setting mechanism of claim 1 wherein during resetting ofsaid drug delivery device, said first component is decoupled from saidsecond component by moving said first component in an axial direction.6. The resettable dose setting mechanism of claim 1 wherein when saiddrug delivery device is used to set the dose of medication, both saidfirst component and said second component rotate together at a samerate.
 7. The resettable dose setting mechanism of claim 1 wherein whensaid drug delivery device is used to inject a set dose of medication,both said first component and said second component rotate and/or movein an axial direction.
 8. The resettable dose setting mechanism of claim1 and further comprising a spindle guide engaged with said spindle,wherein during resetting of said drug delivery device, said spindlerotates while said spindle guide does not rotate.
 9. The resettable dosesetting mechanism of claim 1 further comprising a dose limiter whereinduring resetting of said drug delivery device, said dose limiter isreset to an initial position.
 10. The resettable dose setting mechanismof claim 1 wherein when said drug delivery device is used to inject aset dose of medication, said spindle translates.
 11. The resettable dosesetting mechanism of claim 1 further comprising a cartridge holderreleasably coupled to said resettable dose setting mechanism, whereindecoupling of said first component from said second component iseffected by decoupling said cartridge holder from said resettable dosesetting mechanism.
 12. The resettable dose setting mechanism of claim 1wherein decoupling of said first component from said second component iseffected by an axial movement of said spindle.
 13. The resettable dosesetting mechanism of claim 1 wherein said housing comprises an outerhousing.
 14. The resettable dose setting mechanism of claim 1 whereinsaid housing comprises an inner housing.